| Autor: |
Dutta, Amal K., Khimji, Al-Karim, Songling Liu, Karamysheva, Zemfira, Akiko Fujita, Kresge, Charles, Rockey, Don C., Feranchak, Andrew P. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; 1/1/2016, Vol. 310 Issue 1, pG34-G42, 9p |
| Abstrakt: |
PKC regulates TMEM16Amediated Cl secretion in human biliary cells. Am J Physiol Gastrointest Liver Physiol 310: G34 –G42, 2016. First published November 5, 2015; doi:10.1152/ajpgi.00146.2015.—TMEM16A is a newly identified Ca2-activated Cl channel in biliary epithelial cells (BECs) that is important in biliary secretion. While extracellular ATP stimulates TMEM16A via binding P2 receptors and increasing intracellular Ca2 concentration ([Ca]i), the regulatory pathways have not been elucidated. Protein kinase C (PKC) contributes to ATPmediated secretion in BECs, although its potential role in TMEM16A regulation is unknown. To determine whether PKC regulates the TMEM16A-dependent membrane Cl transport in BECs, studies were performed in human biliary Mz-cha-1 cells. Addition of extracellular ATP induced a rapid translocation of PKC from the cytosol to the plasma membrane and activation of whole cell Ca2 -activated Cl currents. Currents demonstrated outward rectification and reversal at 0 mV (properties consistent with TMEM16A) and were inhibited by either molecular (siRNA) or pharmacologic (PMA or Gö6976) inhibition of PKC. Intracellular dialysis with recombinant PKC activated Cl currents with biophysical properties identical to TMEM16A in control cells but not in cells after transfection with TMEM16A siRNA. In conclusion, our studies demonstrate that PKC is coupled to ATP-stimulated TMEM16A activation in BECs. Targeting this ATP-Ca2 -PKC signaling pathway may represent a therapeutic strategy to increase biliary secretion and promote bile formation. TMEM16A; |
| Databáze: |
Complementary Index |
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